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Eye Surgery And Innovative Technologies (EyeSITe)

Overview:

The Eye Surgery and Innovative Technologies (EyeSITe) programme is led by Principal Investigator Professor Donald Tan Tiang Hwee, Senior Advisor of the Singapore National Eye Centre. He is also the Medical Director of the Singapore Eye Bank. EyeSITe aims to provide new clinical therapies to aid in alleviating ocular morbidity from major eye diseases, including corneal disease, infection, glaucoma, refractive errors and retinal disorders.EyeSITe builds on the strengths of our current TCR flagship programme – TRIOS (Translational Research Innovations in Ocular Surgery), and comprises our 5 most successful programmes in terms of scientific results, clinical outcomes and commercialization potential. EyeSITE will develop novel and innovative approaches to diagnose and treat corneal diseases and glaucoma - 2 of the major causes of blindness worldwide.

Glaucoma is a leading cause of irreversible blindness, affecting approximately 70 million people worldwide - of whom over 6 million suffer from bilateral blindness. In Singapore, glaucoma is the leading cause of irreversible blindness nationwide. Primary angle closure glaucoma, which is more prevalent in Asia compared to primary open angle glaucoma, accounts for most glaucoma-induced blindness.

Corneal disease is the second most common cause of treatable blindness, with 12 million cases recorded globally. Corneal diseases related to eye infections, inflammation, ocular trauma and genetic disorders are major causes of blindness which require corneal transplantation. Even though corneal transplants are largely successful, current surgical outcomes are limited due to long-term graft failure and rejection, resulting in increased morbidity.These programs, if successful, will result in better health outcomes for the above-mentioned ocular conditions, improved medical practice, and may also provide significant economic outcomes to Singapore.

Individual Projects

Theme 1: Antimicrobial Molecules Against Ocular Pathogens

Infectious keratitis (corneal infections) relating to trauma or contact lens wear are a major cause of corneal blindness in Asia, with an estimated 4-6 million blind, and also a major cause of childhood blindness1-4. The indiscriminative usage of broad spectrum antibiotics have resulted in antibiotic resistance emerging throughout Asia, while only one topical antifungal eyedrop preparation (Natamycin) is commercially available to treat fungal keratitis in the region. Methicillin-resistant Staphylococcus aureus (MRSA) and resistant forms of Pseudomonas have also become significant issues. The global antibiotic resistance of gram negative bacteria and MRSAs are two of the most critical healthcare issues in this area. The development of new classes of antimicrobial small peptide and peptoid molecules will have a significant impact in treating corneal infections, and also for systemic infections. Our novel antimicrobials are targeted at 3 major ocular pathogens which also have clinical significance in systemic infections: Pseudomonas spp. (especially antibiotic resistant strains), gram positive organisms (including MRSA), and fungal/yeast infections, all of which are of major public health interest.

Team Members:

Name

Role in Research Theme (e.g. PI, Co-I, Collaborator)

Roger W. Beuerman

Co-PI

Shouping Liu

Co-I

R. Lakshminarayanan

Co-I

Knostatin Pervushin

Co-I

Chandra Verma

Co-I

Swaine Chen

Co-I

Zhou Lei

Co-I

Donald Tan

Co-I

Jodhbir Mehta

Co-I

Theme 2: Novel Ocular Drug Delivery Systems

The development of sustained drug delivery carriers to provide effective prolonged drug release without relying on patient compliance would improve therapeutic outcomes, and improve overall healthcare and disease management – especially for elderly patients. This technology can be applied across other ophthalmic conditions which require chronic medical treatment – our current sustained delivery platforms may be used for a wide variety of drugs and involves drug delivery to the front of the eye for a wide range of anterior segment disorders, which include corneal, glaucoma and uveitic conditions, as well as research into improved sustained delivery of drugs and proteins to the retina.

Team Members:

Name

Role in Research Theme

Tina Wong

PI

Subbu Venkatraman

Co-I

Amutha Barathi

Collaborator

Jodhbir Mehta

Collaborator

Gemmy Cheung

Collaborator

Donald Tan

Collaborator

Tien Yin Wong

Collaborator

Freddy Boey

Collaborator

Theme 3: The Bionic Cornea

Corneal opacification is the second major cause of reversible impaired vision, affecting about 12 million patients globally, with over 50% of the global burden mainly sited in Asia18. Approximately 40% of global corneal blindness cases may be treatable by a corneal transplantation, but it is estimated that only 150,000 transplants are performed globally due to a major shortage of corneas worldwide. Corneal transplant survival rates also vary greatly, with survival rates estimated at 75% and 64% at 5 and 10 years respectively, mostly related to graft endothelial rejection or attrition. Current research efforts are focusing on corneal endothelial biology in an attempt to culture human endothelial cells and also to develop new surgical methods of endothelial keratoplasty, in which the corneal endothelium is selectively transplanted.

The major brunt of corneal disease lies in chronic inflammatory and ocular surface diseases, for which corneal transplantation is contraindicated due to a high failure rate. For these cases, 2 artificial corneas (or keratoprostheses), currently in common use, are preferred. However, current iterations of keratoprosthesis technology are still lacking – both these devices utilize older polymers and outdated designs. The development of a synthetic OOKP-type device not requiring a tooth will significantly improve the time to visual rehabilitation for patients requiring this surgery and simplify the surgical procedure tremendously.

Team Members:

Name

Role in Research Theme

Jodhbir Mehta

PI

Donald Tan

Co-PI

Xiao Wei Tan

Co-I

Gary Peh

Co-I

Roger Beuerman

Co-I

Evelyn Yim

Collaborator

Julie Daniels

Collaborator

Michael Khor

Collaborator

Theme 4: Femtosecond Laser-Assisted Ocular Surgery Systems

Femtosecond ophthalmic surgical lasers are commonly used for corneal refractive surgery. Femtosecond laser technologies are now being explored to perform corneal transplants, and most recently, cataract surgery, bringing higher levels of surgical precision23. Our previous work in TRIOS focused on developing femtosecond laser-assisted corneal stromal refractive lenticules as a by-product of a new corneal refractive procedure: Refractive Lenticular Extraction (ReLEx). ReLEx is a refractive procedure whereby the femtosecond laser incises a refractive lenticule to treat myopia and astigmatism, and the lenticule is removed through a pocket incision (SMILE procedure: SMall Incision Lenticular Extraction). We will investigate the concept of lenticular storage by cryopreservation, and its potential usage in 3 clinical areas: 1) personalized storage for ReLEx patients, which makes the procedure theoretically reversible in the event of complications, 2) storage for use in LASIK patients who have developed keratectasia, or for patients who have keratoconus, who may benefit from implantation of an allograft corneal lenticule, and 3) usage of the lenticules as biological small optic implants for the treatment of presbyopia. If it is successful, lenticular storage provides new treatment strategies for both refractive surgery patients, keratoconics and for all people over the age of forty (presbyopic age).

Team Members:

Name

Role in Research Theme

Jodhbir Mehta

PI

Donald Tan

Co-PI

Soon Phaik Chee

Co-I

Murukeshan Vadakke Matham

Collaborator

Mario Nubile

Collaborator

Theme 5: Stratified Medicine for Primary Angle-Closure Glaucoma

Primary angle closure glaucoma (PACG) is a major cause of visual morbidity and blindness in Asia, and the exact cause of this condition is still unknown. We are developing new ocular imaging techniques with the anterior segment OCT to aid in a pre-emptive diagnosis for this condition. We have identified several novel anatomical risk factors for the development of PACG, which include greater lens vault, greater iris convexity, area and thickness, as well as smaller anterior chamber width, area and volume. We also want to identify individuals who are genetically at risk of developing PACG by a comprehensive genetic analysis scheme to detect the vast majority of the allelic spectrum of PACG disease alleles, which will aid in further stratification of at-risk populations. These studies will endeavor to develop new diagnostic and prognostic approaches to PACG, with a potential novel risk prediction algorithm combining ocular imaging and genetic markers to detect high risk patients (stratified medicine. If successful, the new algorithm will be applicable not only in SNEC, but also at a population-wide level.